Martin-Gayo Enrique, Yu Xu G
Ragon Institute of MGH, MIT and Harvard, Massachusetts General Hospital, 400 Technology Square, Cambridge, MA, 02139, USA.
Curr HIV/AIDS Rep. 2017 Feb;14(1):1-7. doi: 10.1007/s11904-017-0345-0.
Robust HIV-1-specific CD8 T cell responses are currently regarded as the main correlate of immune defense in rare individuals who achieve natural, drug-free control of HIV-1; however, the mechanisms that support evolution of such powerful immune responses are not well understood. Dendritic cells (DCs) are specialized innate immune cells critical for immune recognition, immune regulation, and immune induction, but their possible contribution to HIV-1 immune defense in controllers remains ill-defined.
Recent studies suggest that myeloid DCs from controllers have improved abilities to recognize HIV-1 through cytoplasmic immune sensors, resulting in more potent, cell-intrinsic type I interferon secretion in response to viral infection. This innate immune response may facilitate DC-mediated induction of highly potent antiviral HIV-1-specific T cells. Moreover, protective HLA class I isotypes restricting HIV-1-specific CD8 T cells may influence DC function through specific interactions with innate myelomonocytic MHC class I receptors from the leukocyte immunoglobulin-like receptor family. Bi-directional interactions between dendritic cells and HIV-1-specific T cells may contribute to natural HIV-1 immune control, highlighting the importance of a fine-tuned interplay between innate and adaptive immune activities for effective antiviral immune defense.
目前,强大的HIV-1特异性CD8 T细胞应答被视为在少数实现对HIV-1自然、无药控制的个体中免疫防御的主要相关因素;然而,支持这种强大免疫应答演变的机制尚未完全明确。树突状细胞(DC)是专门的固有免疫细胞,对免疫识别、免疫调节和免疫诱导至关重要,但其在HIV-1控制者的HIV-1免疫防御中可能发挥的作用仍不明确。
近期研究表明,来自控制者的髓样DC通过胞质免疫传感器识别HIV-1的能力有所提高,导致在病毒感染时分泌更强效的细胞内源性I型干扰素。这种固有免疫应答可能有助于DC介导诱导高效抗病毒的HIV-1特异性T细胞。此外,限制HIV-1特异性CD8 T细胞的保护性HLA I类同种型可能通过与白细胞免疫球蛋白样受体家族的固有髓单核细胞MHC I类受体的特异性相互作用影响DC功能。树突状细胞与HIV-1特异性T细胞之间的双向相互作用可能有助于HIV-1的自然免疫控制,突出了固有免疫和适应性免疫活动之间微调相互作用对有效抗病毒免疫防御的重要性。